An Open-Label Phase 1 Study to Investigate the Safety and Maximum Tolerated Dose of INNO-206 (Doxorubicin-6-Maleimidocaproyl Hydrazone; DOXO-EMCH) Administered as a 30 Minute Infusion Every 3 Weeks in Subjects With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- INNO-206
- Conditions
- Malignant Solid Tumour
- Sponsor
- ImmunityBio, Inc.
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Safety
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a phase 1b open-label study evaluating the preliminary safety and maximum tolerated dose of a new formulation of INNO-206 administered at doses of 230 mg/m2, 350 mg/m2 and 450 mg/m2 (165, 260, 325 mg/m2 doxorubicin equivalents, respectively) through intravenous infusion on Day 1 every 21 days for up to 6 cycles.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age between 18 and 70 years, male or female.
- •Histologically or cytologically confirmed malignant solid tumor that has relapsed or is refractory to standard therapy.
- •Subjects who have received prior radiation therapy with stable CNS metastasis with no progression of brain metastasis by CT/MRI scan in last 4 weeks.
- •Capable of providing informed consent and complying with trial procedures.
- •ECOG performance status 0-
- •Life expectancy \>12 weeks.
- •Measurable or evaluable disease according to RECIST 1.1 criteria.
- •Women must not be able to become pregnant (e.g. post menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study.
- •Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.
- •Geographic accessibility to the site.
Exclusion Criteria
- •Palliative surgery, chemotherapy, immunotherapy and/or radiation less than 4 weeks prior to the Screening Visit.
- •Exposure to any investigational agent within 30 days of the Screening Visit.
- •Laboratory values: Screening serum creatinine greater than or equal to 1.5 mg/dL, alanine aminotransferase (ALT) greater than 3 times the upper limit of normal, total bilirubin greater than 3 times the upper limit of normal, white blood cell (WBC) count \< 3500/mm3, absolute neutrophil count \< 2000/mm3, platelet concentration \< 100,000/mm3, hematocrit level \< 33% for females or \< 35% for males, or coagulation tests (PT,PTT) \>1.5 times the upper limit or normal.
- •Clinically evident congestive heart failure \> class II of the New York Heart Association (NYHA) guidelines.
- •Serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V.
- •History or signs of active coronary artery disease with or without angina pectoris.
- •Serious myocardial dysfunction defined scintigraphically (MUGA, myocardial scintigram)or ultrasound determined absolute left ventricular ejection fraction (LVEF) \< 45% of predicted.
- •History of HIV infection.
- •Active, clinically significant serious infection requiring treatment with antibiotics, antivirals or antifungals.
- •Major surgery within 3 weeks prior to treatment.
Arms & Interventions
INNO-206
INNO-206 at dosages of 230, 350, and 450 mg/m2 doxorubicin equivalents of 165, 260, and 325 mg/m2)will be administered as a 30 minute IVI on Day 1 of each cycle.
Intervention: INNO-206
Outcomes
Primary Outcomes
Safety
Time Frame: Up to 6 cycles (every 21 days)
Safety will be based on adverse events, tolerability, physical examinations, vital signs, ECG results, laboratory test results. MTD: If 2 of 5 subjects an any dose level experiences a grade 3 or 4 non-hematologic toxicity, or a platelet count \<25,000/uL or a neutrophil count \<500/uL lasting \>7 days and/or associated with fever \>38.5C, 3 more subjects will be entered at that dose level. If 2 of 3 of the additional subjects experience any of the above adverse events, the dose level immediately below will be identified as the MTD.
Secondary Outcomes
- Objective response rate(Up to 6 cycles (every 21 days))